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Phase I-II study of plitidepsin and dacarbazine as first-line therapy for advanced melanoma

Lookup NU author(s): Professor Ruth Plummer, Professor Alan Calvert

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Abstract

Background: This phase I-II trial compared plitidepsin 1-h infusion alone or combined with dacarbazine (DTIC) 1-h infusion as front-line therapy for advanced melanoma.Methods: The recommended dose (RD) for plitidepsin/DTIC was defined in the first stage. In the second stage, patients were randomised to receive single-agent plitidepsin 3.2 mg m(-2) (n = 20) on days 1, 8 and 15 every 4 weeks (q4wk) or plitidepsin 2.4 mg m(-2) on days 1, 8 and 15 q4wk combined with DTIC 800 mg m(-2) q4wk (n = 38).Results: The overall response rate with plitidepsin/DTIC was 21.4%; all responders had normal serum lactate dehydrogenase (LDH) levels and performance status <= 1 at baseline. Median progression-free survival (PFS) with plitidepsin/DTIC was 3.3 months in all patients, and 4.3 months in those with baseline normal LDH. No responses occurred with single-agent plitidepsin and median PFS was 1.5 months. Both regimens were well tolerated. Haematological abnormalities were more common and transaminase increases more severe with plitidepsin/DTIC. Treatment-related transaminase increases leading to infusion omission on day 8 were relatively common. No drug-drug pharmacokinetic interactions were found.Conclusion: This plitidepsin/DTIC schedule has antitumour activity and manageable toxicity in advanced melanoma. Further evaluation of plitidepsin 2.4 mg m(-2) fortnightly and DTIC 800 mg m(-2) q4wk is recommended.

Publication metadata

Author(s): Plummer R, Lorigan P, Brown E, Zaucha R, Moiseyenko V, Demidov L, Soriano V, Chmielowska E, Andres R, Kudryavtseva G, Kahatt C, Szyldergemajn S, Extremera S, de Miguel B, Cullell-Young M, Calvert H

Publication type: Article

Publication status: Published

Journal: British Journal of Cancer

Year: 2013

Volume: 109

Issue: 6

Pages: 1451-1459

Print publication date: 17/09/2013

Online publication date: 29/08/2013

Acceptance date: 25/07/2013

Date deposited: 05/01/2015

ISSN (print): 0007-0920

ISSN (electronic): 1532-1827

Publisher: Nature Publishing Group

URL: http://dx.doi.org/10.1038/bjc.2013.477

DOI: 10.1038/bjc.2013.477

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